Posted
by
timothy
on Friday February 03, 2012 @11:54AM
from the when-it's-all-greek-to-you dept.

smitty777 writes "Two separate studies by the Taub Institute and Harvard have discovered the pathway used by Alzheimer's Disease to spread through the brain. The studies indicate it's not a virus, but a distorted protein called Tau which moves from cell to cell. Further, the discovery 'may now offer scientists a way to move forward and develop a way to block tau's spread in Alzheimer's patients, said Karen Duff, a researcher at Columbia's Taub Institute for Research on Alzheimer's disease and co-author of one study published Wednesday in the journal PLoS One. "It's enlightening for us because it now provides a whole other area for potential therapeutic impact," said Duff. "It's possible that you can identify the disease and intervene (with potential tau-blocking drugs) before the dementia actually sets in."'"

Does this suggest that it may be hazardous to produce soylent green from Alzheimer's casualties, in the same way that consumption of tissue from animals affected by prion disorders is considered unwise?

I've never heard of anything to suggest that Alzheimers can be "caught." A seminar I saw a few years ago on tau suggested that in order to form these aggregates of tau, you need to have a mutated form of it: normal tau does not start clumping up and killing brain cells (not entirely sure I'm remembering that correctly). It's only transmissible between cells which have the same mutant form of the protein. I don't know, maybe it's possible that material from alzheimers patients could make the disease appear sooner in people with the mutant form who would probably develop symptoms later.

The prion protein that is at the heart of Creutzfeldt–Jakob disease, on the other hand, that appears to be the normal protein misfolding. The diseased proteins seem to convince normal proteins to misfold.

So, as I understand it, the hypothesis is that if you were to inject material from an alzheimer's patient's brain into your brain, for example, the alzheimer's Tau would not cause your tau to start clumping up and would not cause the disease. If you injected brain material from someone suffering from spongiform encephalitis though, the proteins in your brain WOULD be coaxed to start clumping up, causing the disease.

I've never heard of anything to suggest that Alzheimers can be "caught." A seminar I saw a few years ago on tau suggested that in order to form these aggregates of tau, you need to have a mutated form of it: normal tau does not start clumping up and killing brain cells (not entirely sure I'm remembering that correctly).

Right away I also wondered if it was a prion-like issue with malformed tau proteins. Has anyone confirmed whether the structure and orientation (left vs right) of the free tau protein is identical to that of normal tau?

As far as I know tau protein is used to maintain microtubules in cells. Maybe something is damaging the microtubules and the free tau is just a result of this or the tau is malformed to start with and it results in cells dying from defective microtubules.

This particular study was done using Mice so the hypothesis of alzheimer's might be a Prion could be tested without the ethical concern of giving healthy human being alzheimers. Though the Rats of Nimh might object. It would be fairly important to narrow down the search from a rogue Prion you could ingest to a rogue protein your genes instructed to be made.

Alzheimer's is a terrible disease, not just for the person who has it, but especially so for those who are close to the afflicted. The slow, degenerative, wasting of the mind is horrifying to watch, as the person that was once bright and lively gets turned into a shell of their former self. Not able to grasp what's going on around them, or who they're talking to, the person can easily become terrified, lost, and confused, made all the more painful by the fact that they don't know who their children are or why they're here.

I know that identifying the underlying cause and developing a treatment are often worlds apart, but I'm glad nonetheless to see this advancement, if merely for the fact that one day others won't have to experience the pain I did as I watched people I love succumb to Alzheimer's.

Alzheimer's is a terrible disease, not just for the person who has it, but especially so for those who are close to the afflicted. The slow, degenerative, wasting of the mind is horrifying to watch, as the person that was once bright and lively gets turned into a shell of their former self. Not able to grasp what's going on around them, or who they're talking to, the person can easily become terrified, lost, and confused, made all the more painful by the fact that they don't know who their children are or why they're here.

I know that identifying the underlying cause and developing a treatment are often worlds apart, but I'm glad nonetheless to see this advancement, if merely for the fact that one day others won't have to experience the pain I did as I watched people I love succumb to Alzheimer's.

Amen to that.

Last August, my mother was diagnosed with "mild to moderate" Alzheimer's. I had been certain for some time prior to then that she had the disease. She would sometimes repeat as if it had just occurred to her a story she'd told me just minutes earlier, she'd get stuck trying to recall the names of people she'd known for years (such as her 22-year-old granddaughter), and was only strongly confident about the details of events long past. In November, she was examined by two doctors at the Copper Ridge Institute (which is affiliated with Johns Hopkins), which specializes in Alzheimer's research and treatment. She knew the President of the U.S. was black, but couldn't recall his name, thought my youngest sister was 40 (she turned 53 in December), and couldn't remember which day of the week it was (it was Friday).

I call her at least once a week, and she seems to deteriorate more every time I speak with her - and yet, she's still fundamentally the same warm, sweet, vibrant woman she's been as long as I've known her. Just... a little confused. What I fear is that, over time, she will lose all the memories that make her that person. I've known several people with advanced Alzheimer's, and watched them become progressively emptier shells of themselves, until they're little more than slack-jawed zombies, incapable of caring for themselves, or communicating with others - and I don't want to see that happen to my Mom.

But I know it will, because none of these new discoveries will make it out of the lab in time to save her from the ravages of this loathsome disease. And that breaks my heart.

It's like being forced to watch an extremely bad car crash in slow motion - so slow it takes place over the course of years rather than seconds. You know what's happening from quite early on in the process, you've got a pretty good idea of how it's going to pan out in the end, you can tell from the pace at which things progress that the end may be some time away and you're powerless to stop it.

Exactly. My mom just died last November, after languishing in a nursing home for 10 freakin' years with it. It's surprising she lasted that long, because she was pretty bad off when my dad put her in. (He died 5 years later.)
In those last years, she was pretty much a zombie, or a human shell, hadn't made a coherent sentence in years, and finally stopped even trying to speak a single word.. she seemed to sleep a lot, but I don't know everything that happened when I wasn't visiting. She so didn't deserve

Thomst: I feel for you. My mother developed Alzheimer's some years ago and died from it. If you have not read The 36 Hour Day, you may want to get it. Understanding your mother's humanity and growing lack of control over her own life are the most important things you can use to help her. I was very lucky in being of a mind not to try to change my mother's behavior, and instead to help her experience as complete a life as she could.

I'm sorry for your loss.

I'm not familiar with The 36 Hour Day, but I'm acutely conscious of my Mom's state of mind, and the fear and depression I know she's experiencing as her disease progresses. I try to be as supportive as possible, without becoming maudlin, whenever I speak to her. Lately, I've been urging her to record her memoirs as a legacy for her yet-unborn grandchildren. (It's something she's talked about doing for years, so it's really her idea, not mine.) I just want her to

It is a truly evil disease. I think my mom was going down that path so when she died almost instantly from a massive stroke I saw it as a bit of a blessing for everyone. Beats watching her soul slowly get scooped out of her (and probably hellish for them too).

I don't have anything insightful to add, but I feel compelled to say fuck you, cancer and double fuck you, Alzheimer's. Thank you for your attention.

Heh...yeah. Every single person in my family for the past 3 generations, with only two exceptions, both maternal and paternal has died in their early 70's or before from cancer. The exceptions: one of my cousins committed suicide, and one of my grandfathers survived into his 80's only to succumb to Alzheimer's. I got to watch a truly brilliant man, who I've always considered far more intelligent than I, become unable to understand the most simple concepts, followed by slowly becoming more and more unres

I don't mean to pry, but why on Earth would your mother refuse chemo? These days most cancers (not all, by any means, but most) are extremely treatable and survivable if caught early. It's unpleasant for a few months, but with a few exception you'll mostly always survive and be fine. It's not like it was 30 years ago where you were looking at 50-50 odds at best and the treatment was worse than the disease. I personally know literally half a dozen cancer survivors just among my family and people that I a

It's much easier to successfully treat cancer in its early stages. Which is great if you're "lucky" enough to be struck down with a type that tends to be easily detectable at early stages. Testicular and breast cancer fall into this category - it's pretty damn obvious if you've got a lump on one of your testicles.

Cancers that start deep inside the body - things like lung, liver, pancreas cancer - often don't show much in the way of symptoms until you're at a pretty advanced stage.

You're right about the stages, also the type of cancer. I know at the local relay for life events I'll hear 'Oh my cancer's been in remission for years' and then the next person will tell you how a family member was gone in months. I also hear a lot of stories at the chemo ward. My mother's been fighting ovarian for over 3 years, but it had recently spread to her liver. Actually her doctors told her in December to get her affairs in order as there was nothing they could do, probably last 2-3 months. Also sh

I suppose I should have been more specific. Certainly there are form of cancer, or stages of cancer, where accepting treatment is simply an uncomfortable way to prolong the inevitable. The implication in the GGP though is that his mother is deliberately avoiding doctors and potential diagnosis, because she intends to refuse treatment under almost any circumstances. It's one thing to rationally look at your options, realize that you have stage four small cell lung cancer, and extending your life for a few

That was my first thought too. Knowing what little I do of him, he'd probably be the first in line to volunteer for human experimental studies of this.

And not out of selfishness, but to benefit others with his experience.

I have attended a few of his readings, over the past 6 years and he had first explained he thought he'd suffered some kind of minor stroke, the following year he came through town with another reading and shed more light on his experience. Finally there was the "embuggerance" note posted publicly after the diagnosis of Early Onset Alzheimer's. He has tried many treatments and has been advocating Right To Die.

It was done at a University by students who probably weren't paid. It wasn't done by a pharmaceutical lab. Remember that when the drug companies try to justify charging your parents $2000 for a one month supply of Alzheimer medication.

While I agree that the pharmaceutical businesses is a complete disaster area in terms of cures-per-dollar, you can't point at one publicly funded study and use it as evidence of that fact. It's spectacularly irrational.

While I agree that the pharmaceutical businesses is a complete disaster area in terms of cures-per-dollar, you can't point at one publicly funded study and use it as evidence of that fact. It's spectacularly irrational.

Uh, yes you can. Not on its own, but in conjunction with a larger body of studies that all demonstrate this point. It's not a smoking gun, it's just part of a larger body of evidence. But go ahead and call it "spectacularly" irrational if you want, I guess.

The last ten years have not been a good time for the metaphorical pipeline. I'm not sure what's goign to replace it - startups, spinoffs, and publicly funded grand challenges, probably - but business isn't cutting it.

You can't get approval from the FDA without showing some very specific pharmacology data. You need to show you know exactly what's going on at the lowest level or there's not a chance in bureaucracy that CBER or CDER is going to approve your new drug application. Theses days even the small molecule generics have to at least make a facsimile of the big boy's mechanism description and pay for someone on staff qualified to answer questions about it.

We shouldn't trust pharmaceuticals, that's for sure. Between the questionably ethical testing in 3rd world countries, the highway robbery, the lobbying to the medical industry to push fairly worthless products, and, oh yeah, their old-fashioned bribery (I mean lobbying) of elected officials to keep their racket going, they are evil. I got laid off from Pfizer two days after Christmas years ago, so I'm not on their side.

Still, I have to point out that basic biological research is a different beast from true medical research. Clinical trials in people are generally very expensive compared to basic research. They take much longer too. Mass producing drugs is not cheap to begin with, and the standards have to be very high for pharmecuticals. 70% purity of a drug you're going to inject into rats to test the effect for basic research like this is acceptable often, but that's hideously impure for something you're going to be putting into people.

The biggest disadvantage pharmecuticals have is liability. No one sues you if one of your lab rats or plates of cells die, this is not the case if someone taking your medicine dies. You need to hire an army of lawyers.

They do have huge costs, and the risks are much higher. Again, they should be scrutinized, but I don't think it's fair to imply that just because a university lab has a result on Alzheimers means that drugs should be cheap.

I hate this statement as a statement against the pharmaceutical industry.

Marketing 101 is all about Return on Investment. Marketing is an investment from which you expect a return greater than the investment. Very few large companies spend more on marketing than they get back out of it. This is just as true for pharmaceuticals as it is any other industry. That is the POINT of marketing expenditure. Maybe some companies have marketing departments which suck at their job. But that's not a problem with m

No, the problem is that the drug companies have NOT been producing 'useful' drugs. They have mostly (of course, there are a few exceptions) been producing 'me too' drugs. Yet another acid blocker for your tummy ache, yet another ACE inhibitor for your blood pressure, yet another minimally modified anti depressant for everything else.

So when you don't have biology to tout, you bang on the advertising table. Put up pretty graphs about how much better your drug is than the existing drug and hope nobody noti

Not that I'm a big fan of the way the Pharmaceutical Industry works these days, but its a lot less black and white than you suggest. Drug companies pay fellowships for students going to grad schools, sponsor labs and give grants to Chemical Engineering departments who publish work like this, and do their best to ensure a continued flow of talent and research. There is Federal grant money in there as well. Once the research is done, Chemical Engineers at the drug companies work on how to reproduce and mas

And if there isn't a generic available, one can be thankful someone took a very high risk of being able to make a lot of money in a short window selling just what was needed when nobody else had taken that chance before. It may not be the purist altruism, but it eases discomfort or saves life to the point where people are willing to buy it.

While I'd love to see some reform of the drug industry, it isn't quite as black-and-white as you make it out. First, all they discovered is a disease mechanism, not a treatment.

When somebody does come up with a proposed treatment, it will be after some modest amount of R&D money is spent (might be a lot, might be a little - chances are the study that nails it won't be expensive but all the work that didn't pan out will be). Now you have a drug candidate - a molecule that in a test tube does something

It was Daniel Gajdusek and Michael Alpers that showed that Kuru could be transmitted by brain material. Margaret Mead was not in this part of Papua New Guinea, and Kuru is not the same as CJD (although both are prion diseases with similar effects).

We've known about tau protein's involvement in Alzheimers for decades. Specifically, we've known that the protein forms tangles which crush brain cells. That part is beyond old news. What seems to happen is that the tau protein "unzips" from its proper location, resulting in brain cells registering that there is insufficient tau protein in locations where it should be, in turn resulting in a loop that will kill everything in the area.

What is NOT known is why it unzips. My father's work in the late 80s, early 90s, showed that aluminum toxicity can cause the unzipping process. Later studies have shown that this is not the only pathway, but that there is usually something encased in the tau protein.

This has led to me speculating that this may have once been a feature, not a bug, that in early life this might have been an environmental detox mechanism (bind toxic chemicals in the area up in protein which is then ejected). This is based on the fact that the brain is unique amongst cells utilizing tau protein in that it has nowhere to eject bound-up toxins and that you don't see these kinds of tangles forming in other contexts where tau protein exists. It would also explain why Alzheimer's looks like it could be virally caused as it would end up with the same look and feel at the neurological level. On the one hand, I've read the papers, I've been involved in the research, I understand the science extremely well. On the other hand, neuroscience is a jealous discipline - even biochemists have a very tough time getting a hearing and I've far less standing than that in the biological sciences - and thus I do not expect this speculation to get looked at. (And, no, this speculation isn't Wikipedia-based. The original thoughts were written up when Gopher was the protocol of choice and really is based on hard, raw data collected in the field. I was, after all, involved in collecting it.) Nonetheless, this finding convinces me that I will prove to have been far closer to the actual mechanism than most of the recognized theories to date. (Yes I'm an old, arrogant, snobbish fart. Now fetch me a lawn so you can gerroff it!)

That was his own fault. He decided to try homeopathic voodoo instead of sound, scientifically-validated methods to treat his cancer initially. That resulted in an early diagnosis (with high probablity of complete remission) turning into a late treatment (with far less favorable odds). The key with most agressive cancers is early diagnosis AND early treatment.

Cases like this are where homeopathy changes from being mostly harmless, and therefore not worthy of much attention, and become outright dangerous.

According to his biography, the doctors and nurses in the OR when he had his tumor biopsied the first time started crying when they realized that he had the much rarer, and treatable form of pancreatic cancer.

Jobs was a well educated, intelligent man sounded by well educated, intelligent people with a vested financial interest in keeping him alive. I seriously doubt he based his entire treatment off Joe Bob's Snake Oil Voodoo and Cancer Treatment Center of the Internet and Wishful Thinking. Rather, I'm sure he looked at his options and made a personal decision based on his personal wishes and situation. His treatment was his own personal choice. The decision was not pushed on him nor was he ill-informed. I'

Being intelligent doesn't stop you from being wrong. Steve Jobs' choice was indeed his own, but it was a stupid choice and a wrong choice that he himself later admitted was going to kill him. In his case, his arrogance overrode his intelligence, and he admitted as much. Having said that, his knowledge of cancers was probably extremely limited. Intelligence doesn't grant you skills or knowledge, it merely grants you the ability to attain them faster -- within certain constraints. Intelligence is often limite

Jobs might have been well-educated and intelligent, but he was fundamentally a salesperson. A very high-powered one. They tend to be crazy. It's usually a fairly specific kind of crazy, but crazy nonetheless. Basically, their success leads them to believe that they can accomplish anything just by force of will and personality. These people are heavily into all that self-actualization motivational stuff. They also really _believe_ in it due to their own success. Confirmation bias leads them to believe that t

According to his biography he simply denied to himself that he had cancer. He was afraid of surgery, a long time believer in the use of fad diets to reach enlightenment, cure disease and render one's body odor nonexistent, and had a near super-human ability to ignore reality (RDF). He tried a fad diet, championed by a renowned snake-oil salesman of an alternative physician, and wasted valuable time. In the end though, he aggressively pursued what ever science-based treatments were available to him and op

Well, he wasn't cured, but he lasted a remarkably long time, and managed to get a liver transplant that was very questionable given that he was dying of pancreatic cancer. Usually they don't give organ transplants to people with such a bad prognosis. Getting the liver may have extended his life by about 2 years. It very well could have extended a different patient's life by twenty. He managed to get the liver by spending a lot of money to fly around and visit a lot of different doctors and get on a lot of d

I'm always suspicious of these 'breakthroughs' when they are introduced via mass media. Somebody thought up a possible cause always gets interpreted to mean that there must be a cure on the way and that's a sexy story to sell the papers, so... Where are the links to peer-reviewed scientific journals? This is Slashdot, a link to the NY Times isn't much more than a start.

I talked with the researchers involved with Folding@Home, and they told me that indeed, processing power is at least partly used to research Tau protein misfolding.

So, if you want to do something good for your future (since there is a good chance you'll be hit by Alzheimer's if you live long enough), I suggest contributing your CPU and graphics cards cycles to Folding@Home.

Nice that they've isolated it down to a single protein causing the problem. From what I gathered from the article the protein is supposed to provide the insulation between neural networks as you get older. Shouldn't be long then before they have it isolated down to the gene sequence that causes the protein to go rogue in the first place. Assuming that it's genetic and not some other kind of Prion.

The Tau protein has been known to be involved with Alzheimer's Disease for a long time. For a long time the accumlation of beta amyloid has been thought as the main driving mechanism of Alzheimer's Disease. The Tau-hypothesis has been around for a long time as well. I get the impression that the majority of the research on Alzheimer's Disease has been on beta-amyloid, including finding medication that is targeting this protein. And large sums of money has been invested in this research. I don't know if this

No, it isn't. The protein is similar and has similar infectivity characteristics, but no-one has proved that you get vCJD from eating meat from cattle that had BSE. The old story: correlation is not causation. There is still nothing to prove there was not a common cause.

Given that Alzheimer's was diagnosed over a hundred years ago I'd doubt that anything that we've been doing recently would actually be the source of the problem. Alzheimer's has probably been around for a very long time just was identified as old people going senile. It could easily be a Prion as you're implying with comparing it to Mad Cow disease, and it could be that something we are doing is spreading it. However, it could easily be just a genetic defect that's causing the protein to be folded incorre